Uridines Modified with Sulfur or Selenium in U-G Wobble Pairs Matter for tRNA Function

Transfer RNAs (tRNAs) are ubiquitous in cells and are essential for the translation of genetic information from messenger RNA (mRNA) into proteins in all three domains of life. They act as adaptors that decode mRNA codons via their anticodons and deliver the corresponding amino acids to the growing polypeptide chain. Currently, over 100 modified nucleosides have been found in tRNA that are crucial for the integrity and functionality of this molecule. Almost half of them are located at position 34 of the anticodon, which is commonly referred to as the "wobble" position. In this review, we highlight the sulfur- and selenium-modified uridines at this position and discuss their physicochemical properties and regulatory functions in gene expression. We examine how the tRNA anticodons accomplish the decoding of synonymous codons, particularly 5'-NNA- 3' and 5'-NNG-3', and provide efficient uridine-adenosine and uridine - guanosine base pairing. We also analyze the effects of C5 substituents on the tautomeric behavior and ionization properties of 2-thiouridines and 2-selenouridines. Theoretical calculations on the stability of 5-substituted uracil - guanine base pairs and their structural representation in crystal complexes of tRNA-mRNA-ribosomes emphasize the importance of these modifications in fine-tuning translation fidelity and efficiency.